The RSDA candidate proposes to extend his research in the areas of behavioral genetics and neuroimaging by focusing on the neurodevelopmental pathways leading to neuropsychiatric disability in individuals with the fragile X (fra X) mutation. In order to elucidate these pathways, the research will assess (1) the extent to which the fra X mutation is a cause of behavior, learning and developmental dysfunction in children, (2) the particular pattern of neuropsychiatric dysfunction caused by this genetic condition and, (3) the specific neuroanatomical variations and molecular factors associated with the severity of this dysfunction. Obtaining information relating to the neurodevelopmental pathways leading to neuropsychiatric disability in the fra X syndrome is of importance from the standpoint of understanding linkages between gene, brain and behavior. The chance to study a group of children with a homogeneous etiology for their neuropsychiatric and developmental disability is a rare opportunity in child psychiatry or developmental research. More specifically, relating fundamental molecular events to specific neuropsychiatric and neurobiological variables opens the possibility of establishing direct links between genetic etiology and the pathogenesis of developmental and psychiatric dysfunction. Although this information will have specific benefit to fra X syndrome, it will also have broader relevance to the understanding of how genetic-biological pathways lead to particular profiles of neuropsychiatric disability in children. The proposed research is designed to expand the RSDA candidate's knowledge, research skills and collaborative relationships in the areas of molecular genetics, neuroimaging developmental disabilities and classification in child and adolescent psychiatry.